oaz1基因对慢性粒白血病k562细胞红系分化与凋亡作用的研究

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1、硕士学位论文Effectofornithinedecarboxylaseantizyme1ontheerythroiddifferentiationandapoptosisofCMLcelllineK562Name：WuBing-pingSupervisor：Prof．MaWen-liAssociateResearcherJiangLiABSTRACTOrnithinedecarboxylaseantizyme(OAZ)，wasfirstknownasthenegativeregulatorofOrnithinedecarboxylase(ODC，rate—limitingenzymeofth

2、epolyaminebiosyntheticpathway)．EctopicexpressionofOAZinsolidtumorreducemalignantproliferation，inducecellcyclearrest，demonstrateitsanti—tumorabilityandpotentialvalueastumortherapeutictarget．Sofar,theunderstandingofOAZfunctionmechanismmainlyfocusonthefollowingthreeaspects．First，thereisanuniqueffameshi

3、ftmechanismduringthetranslationprocessofOAZ，thatiswhenribosomecometotheterminationcodonofORF1(TCCTGATG)，polyaminecouldregulateitcontinuethetranslationprocessbymovingonebaseforwardSOastotranslateintoanactiveantizyme．Therefor,wemodifiedtheframeshiflsite(TCCTGATG---}TCCGATG)SOastoeliminatetheinterferen

4、ceeffectarosefromallogenicmaterials．Second，OAZfunctionasahubinregulatingpolyaminehomeostasis．OAZbindtoODCwithhighaffinityandthentargetODCto26Sproteasome，induceitsdegradationinanubiquitin-independentmanner．OAZmayalsoregulatepolyaminetransportcarrieronthemembrane，reducingcelluptakeofexogenouspolyamine

5、andpromotingitsdischarge．TheadjustmentofpolyaminehomeostasiscausedbyOAZfinallyABSTRACTparticipateinvitalcellactivities．Finally,theubiquitin-independentdegradationmannerinducedbyOAZisalsooccurinsomeotherimportantcellularmacromolecules，suchascyclinD1，SmadlandAuroraAkinase，suggestingitshouldbeonekeymec

6、hanismforOAZtoparticipateinregulatingcellfunctions．Chronicmyeloidleukemia(CML)，amalignantcloningdiseasesderivedfromhematopoieticstemcell，characterizedbythebalancedreciprocaltranslocationofchromosomes9and22(t(9；22)(q34；ql1))，generatinganenhancedBCR／ABLtyrosinekinaseoncoprotein．Itinterferenormalcellpr

7、ocessbyspontaneousfunctionthroughmultiplesignaltransduction，resultingintheinhibitionofcelldifferentiationandthetoleranceofcellapoptosis，itisresponsibleforthepathogenesisofCML．Withthein—depthstudyoftum